First Evidence of a Polygenic Susceptibility to Pain in a Pediatric Cohort

BACKGROUND:There is currently no evidence about the genetic bases of postoperative pain variability in children. METHODS:We prospectively followed a cohort of 168 children after orthopedic or abdominal surgery, who were under morphine patient-controlled analgesia. The children and their parents were genotyped for 6 candidate-gene polymorphisms (single-nucleotide polymorphisms [SNPs]) implicated in nociception and opiate metabolism: ABCB1C3435T, COMTVal158Met, NTRK1His40Tyr, OPRMA118G, POMCArg236Gln, and a haplotype of CYP2D6. Postoperative pain was assessed using the Faces Pain Scale (FPS), at rest and during mobilization, 11 times during the first 24 postoperative hours. RESULTS:At rest, and to a lesser extent, at mobilization, having at least 4 pain peaks of FPS score >6 in 24 hours was more frequent in children with ABCB1_CC than in children with ABCB1_CT and ABCB1_TT (adjusted risk ratio = 4.5; 95% confidence interval [CI],1.5–13.4; corrected CI for multiple comparisons, 0.98–20.55) and was more frequent in children with OPRM_GA than those with OPRM_AA (adjusted risk ratio = 3.5; 95% CI, 1.1–11.2; corrected CI, 0.70–17.30). After adjusting for parental mating type and correcting for multiple comparisons, mean FPS scores across the 24 postoperative hours were higher for OPRM_GA than for OPRM_AA at rest (P < 0.0002), higher for NTRK1_ CT or NTRK1_ TT than NTRK1_ CC during mobilization (P = 0.002), and lower for COMT_GG than COMT_AA and COMT_GA, during mobilization (P = 0.005). CONCLUSIONS:ABCB1 and OPRM genotypes are associated with clinically meaningful pain variability, whereas NTRK1 and COMT are linked to subclinical effects. This first but small cohort study provides clues to further explore the genetic foundations of pediatric pain.

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